Russian Heart Failure Journal 2010year Influence of candesartan and its combination with spironolactone on left ventricular diastolic function and level of collagen balance’s biochemical markers in patients with chronic heart failure and preserved left ventricular systolic function

Influence of candesartan and its combination with spironolactone on left ventricular diastolic function and level of collagen balance’s biochemical markers in patients with chronic heart failure and preserved left ventricular systolic function

Background. The reason of CHF development is mostly LV diastolic dysfunction (DD). The main cause of high LV filling pressure is reduction of myocardial susceptibility due to increased number of collagen fibers (myocardial fibrosis). Objective. To evaluate the effect of angiotensin receptor blocker (ARB) candesartan and aldosterone antagonist spironolactone on LV diastolic function and level of biochemical markers of collagen balance in patients with CHF and preserved systolic function. Materials and methods. 69 patients with CHF and LVEF >45 % were randomised to 2 groups: candesartan monotherapy (n=35, 32 mg / day) and its combination with spironolactone (n=34, 25 mg / day). Examination was performed at baseline and in 6 months, and included in addition echocardiography (LV diastolic function assessment) and laboratory analyses to determine NT-proBNP blood level and biochemical markers of collagen balance. Results. Combination therapy with candesartan and spironolactone led to significant decrease of average CHF FC and NT-proBNP blood level in comparison with candesartan monotherapy. Significant increase of E / E´ and E / Vp ratio (p<0.05) was observed just in the group of candesartan mono­therapy. Candesartan did not influence collagen balance: indicators of collagen synthesis (PIP) and its decomposition (MMP‑1, TIMP-1 and CITP) remained practically unchanged. Combination therapy did not affect collagen synthesis (PIP level stayed unchanged), but accelerated its decomposition (decreased TIMP-1 and increased CITP levels, p<0.05). The most significant difference between groups on functional status, LV diastolic function and markers of collagen balance was observed in patients with baseline severe DD or atrial fibrillation. Thus, combination therapy with candesartan and spironolactone in patients with CHF and relatively preserved systolic function led to reversal of myocardial fibrosis, slowing of LV DD progression and clinical status improvement in comparison with candesartan monotherapy. These effects were more obvious in subgroup of patients with severe DD and atrial fibrillation.